Following reports of enhanced humoral immunity to Saccharomyces cerevisiae in patients with Crohn's disease, and identification of an immunodominant, high molecular weight glycoprotein (gp200), we have investigated the cellular immune response to this yeast in normal individuals. Following exposure to a crude saline extract (Sacc), peripheral blood mononuclear cells (PBMC) from these subjects demonstrated dose-dependent increases in tritiated thymidine incorporation, the time-course of which resembled that of the response to the known recall antigens PPD and TT. This was accompanied by increased cytotoxicity of the cultured cells for natural killer (NK)-sensitive and NK-resistant target cell lines. Furthermore, using a purified, high molecular weight, glycoprotein fraction of Sacc in culture, a dose-dependent lymphoproliferative response was again observed. Stimulation indices (SI) for thymidine incorporation by umbilical cord blood lymphocytes exposed to Sacc were low compared with those of normal adults. These results provide evidence for possible antigen-specific, cellular, immune sensitization of normal individuals to a ubiquitous dietary component.